Prdm6-KO Mouse

Prdm6, a member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors, has diverse essential functions. It is involved in multiple biological processes such as heart development, neural crest cell (NCC) differentiation and migration, and may play a role in vascular precursor differentiation [2,5,6]. In the context of diseases, it has associations with medulloblastoma, hypertension, and congenital heart diseases [1,4]. Genetic mouse models have been crucial for studying Prdm6's functions.

In mouse models, disruption of Prdm6 in NCCs led to impaired CNCC differentiation, delamination, and migration, resulting in patent ductus arteriosus (DA) and ventricular non-compaction [2]. SMC-specific depletion of Prdm6 during development caused perinatal lethality and a patent DA phenotype, along with reduced DA tone and contractility [3]. Conditional deletion of Prdm6 in the smooth muscle cell lineage led to perinatal lethality due to lung hemorrhage [5]. In human hindbrain neuroepithelial stem cells, Prdm6 expression promoted medulloblastoma, though the resulting tumors matched human Group 3 rather than Group 4 medulloblastoma [1]. In mice, heterozygous disruption of Prdm6 under the control of the smooth muscle cell protein 22-α promoter led to salt-induced systemic hypertension [4].

In summary, Prdm6 is a key regulator in heart development, NCC-related processes, and vascular function. Its dysregulation is associated with congenital heart diseases, medulloblastoma, and hypertension. Studies using gene knockout (KO) and conditional knockout (CKO) mouse models have been instrumental in revealing these functions and disease associations, providing potential therapeutic targets for these conditions.

References:

1. Schmidt, Christin, Cohen, Sarah, Gudenas, Brian L, Weiss, William A, Schwer, Bjoern. 2024. PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression. In Scientific reports, 14, 16074. doi:10.1038/s41598-024-66811-6. https://pubmed.ncbi.nlm.nih.gov/38992221/

2. Hong, Lingjuan, Li, Na, Gasque, Victor, van Dijk, David, Mani, Arya. 2022. Prdm6 controls heart development by regulating neural crest cell differentiation and migration. In JCI insight, 7, . doi:10.1172/jci.insight.156046. https://pubmed.ncbi.nlm.nih.gov/35108221/

3. Zou, Meng, Mangum, Kevin D, Magin, Justin C, Furey, Terrence S, Mack, Christopher P. 2023. Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility. In JCI insight, 8, . doi:10.1172/jci.insight.163454. https://pubmed.ncbi.nlm.nih.gov/36749647/

4. Gunawardhana, Kushan L, Hong, Lingjuan, Rugira, Trojan, Noonan, James P, Mani, Arya. 2023. A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. In The Journal of clinical investigation, 133, . doi:10.1172/JCI160036. https://pubmed.ncbi.nlm.nih.gov/36602864/

5. Gewies, Andreas, Castineiras-Vilarino, Mercedes, Ferch, Uta, Dyer, Martin J S, Ruland, Jürgen. 2013. Prdm6 is essential for cardiovascular development in vivo. In PloS one, 8, e81833. doi:10.1371/journal.pone.0081833. https://pubmed.ncbi.nlm.nih.gov/24278461/

6. Wu, Yaxu, Ferguson, James E, Wang, Hong, Wang, Hengbin, Patterson, Cam. 2007. PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation. In Journal of molecular and cellular cardiology, 44, 47-58. doi:. https://pubmed.ncbi.nlm.nih.gov/17662997/